Pharmacokinetic aspects of rectal formulations of Temazepam

Abstract

An in vitro/in vivo study was carried out with different rectal formulations of temazepam. Pharmacokinetic data were determined in a cross-over study in 10 volunteers after rectal administration of 10 mg temazepam as a polyethylene glycol based suppository (selected from in vitro data), a liquid-filled capsule and a micro-enema respectively, using oral administration of a liquid-filled capsule as a reference. Serum levels of temazepam indicate an instantaneous and complete release from the micro-enema (Frel=0.94±0.21, Cmax 205±36.9 μg/l, tmax 0.49±0.31 hour) and a slower but complete release of temazepam from the suppository (Frel=1.01±0.25, Cmax 202±41.3 μg/l, tmax 1.48±0.41 hour). A high interindividual variation in absorption profiles was observed after rectal administration of the liquid-filled capsule (Frel 0.72±0.36, Cmax 182±122 μg/l, tmax 4.08±4.28 hour), which makes it less suitable for rectal use. The micro-enema and suppository appear to be useful as rectal formulations for temazepam.